scholarly journals Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis

2015 ◽  
Vol 57 (6) ◽  
pp. 917-924 ◽  
Author(s):  
George Thanassoulis
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Drug Target ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Lipoprotein A ◽  
Novel Drug

scholarly journals Metabolomics in Severe Aortic Stenosis Reveals Intermediates of Nitric Oxide Synthesis as Most Distinctive Markers

2021 ◽  
Vol 22 (7) ◽  
pp. 3569
Author(s):  
Beau Olivier van van Driel ◽  
Maike Schuldt ◽  
Sila Algül ◽  
Evgeni Levin ◽  
Ahmet Güclü ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Surgery ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Western Blot ◽  
Aortic Valve Disease ◽  
Metabolic Profile ◽  
Valve Disease ◽  
Healthy Controls ◽  
Calcific Aortic Valve Disease

Background: Calcific aortic valve disease (CAVD) is a rapidly growing global health problem with an estimated 12.6 million cases globally in 2017 and a 112% increase of deaths since 1990 due to aging and population growth. CAVD may develop into aortic stenosis (AS) by progressive narrowing of the aortic valve. AS is underdiagnosed, and if treatment by aortic valve replacement (AVR) is delayed, this leads to poor recovery of cardiac function, absence of symptomatic improvement and marked increase of mortality. Considering the current limitations to define the stage of AS-induced cardiac remodeling, there is need for a novel method to aid in the diagnosis of AS and timing of intervention, which may be found in metabolomics profiling of patients. Methods: Serum samples of nine healthy controls and 10 AS patients before and after AVR were analyzed by untargeted mass spectrometry. Multivariate modeling was performed to determine a metabolic profile of 30 serum metabolites which distinguishes AS patients from controls. Human cardiac microvascular endothelial cells (CMECs) were incubated with serum of the AS patients and then stained for ICAM-1 with Western Blot to analyze the effect of AS patient serum on endothelial cell activation. Results: The top 30 metabolic profile strongly distinguishes AS patients from healthy controls and includes 17 metabolites related to nitric oxide metabolism and 12 metabolites related to inflammation, in line with the known pathomechanism for calcific aortic valve disease. Nine metabolites correlate strongly with left ventricular mass, of which three show reversal back to control values after AVR. Western blot analysis of CMECs incubated with AS patient sera shows a significant reduction (14%) in ICAM-1 in AS samples taken after AVR compared to AS patient sera before AVR. Conclusion: Our study defined a top 30 metabolic profile with biological and clinical relevance, which may be used as blood biomarker to identify AS patients in need of cardiac surgery. Future studies are warranted in patients with mild-to-moderate AS to determine if these metabolites reflect disease severity and can be used to identify AS patients in need of cardiac surgery.

scholarly journals Correlations between lipoprotein(a) gene polymorphisms and calcific aortic valve disease and coronary heart disease in Han Chinese

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096535
Author(s):  
Hongzhi Dong ◽  
Hongliang Cong ◽  
Jing Wang ◽  
Yiyao Jiang ◽  
Chao Liu ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Density Lipoprotein ◽  
Han Chinese ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Lipoprotein A ◽  
Minor Alleles

Objective To investigate the relationship between lipoprotein(a) gene ( LPA) polymorphisms and calcific aortic valve disease (CAVD) and coronary heart disease (CHD) in Han Chinese. Methods A total of 148 patients were recruited (n = 71 with CAVD and n = 77 with CHD) based on a diagnosis achieved using color Doppler echocardiography, coronary angiography, or computed tomography angiography. Seventy-one control individuals without CAVD or CHD were also recruited. Biomarkers including levels of lipoprotein(a) [Lp(a)], low-density lipoprotein and high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B were tested. LPA polymorphisms rs10455872, rs6415084, rs3798221, and rs7770628 were analyzed using SNaPshot SNP. Results Lp(a) levels were significantly higher in CAVD and CHD groups compared with controls. There was no significant difference in the allelic frequency distribution of rs3798221, rs7770628, or rs6415084 between CHD, CAVD, and control groups. Linear regression showed that rs3798221, rs7770628, and rs6415084 were associated with increased Lp(a) concentrations. Two CAVD patients among the 219 participants carried AG minor alleles at rs10455872, while the remainder carried AA minor alleles. Conclusion rs3798221, rs6415084, and rs7770628 polymorphisms within LPA are associated with higher Lp(a) plasma levels, which correlate with increased CAVD and CHD risks.

scholarly journals Evaluation of Lipoprotein(a) Electrophoretic and Immunoassay Methods in Discriminating Risk of Calcific Aortic Valve Disease and Incident Coronary Heart Disease: The Multi-Ethnic Study of Atherosclerosis

2017 ◽  
Vol 63 (11) ◽  
pp. 1705-1713 ◽  
Author(s):  
Jing Cao ◽  
Brian T Steffen ◽  
Weihua Guan ◽  
Matthew Budoff ◽  
Erin D Michos ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Incident Coronary Heart Disease ◽  
Lipoprotein A ◽  
Ethnic Study ◽  
Lower Limits

Abstract BACKGROUND A number of lipoprotein(a) [Lp(a)] analytical techniques are available that quantify distinct particle components, yet their clinical efficacy has not been comprehensively evaluated. This study determined whether Lp(a) mass [Lp(a)-M], Lp(a) cholesterol content [Lp(a)-C], and particle concentration [Lp(a)-P] differentially discriminated risk of calcific aortic valve disease (CAVD) or incident coronary heart disease (CHD) among 4679 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS Lp(a)-M, Lp(a)-C, and Lp(a)-P were measured in individuals without clinical evidence of CHD at baseline. Relative risk regression and Cox proportional analysis determined associations between Lp(a) and the presence of CAVD or 12-year risk of CHD, respectively. To control for the relatively high lower limits of quantification for Lp(a)-C and Lp(a)-P assays, the upper 25th and 15th percentiles were selected as analytical cutoff points. RESULTS Regardless of method or analytical cutoff, high Lp(a) concentrations were significantly associated with CAVD and CHD in MESA participants following adjustment for typical cardiovascular risk factors. Stratifying by race/ethnicity rendered most associations nonsignificant after correction for multiple comparisons, but Lp(a) remained associated with CAVD in whites irrespective of method (all P < 0.0001). CONCLUSIONS Associations of Lp(a)-C, Lp(a)-P, and Lp(a)-M with CAVD or incident CHD were similar in this entire MESA sample using a dichotomized statistical approach. However, the high lower limits of quantification and imprecision of the Lp(a)-C and Lp(a)-P assays limited their usefulness in our analyses and would likely do so in research and clinical settings.

scholarly journals Lipoprotein(a) Levels Are Associated With Subclinical Calcific Aortic Valve Disease in White and Black Individuals

2016 ◽  
Vol 36 (5) ◽  
pp. 1003-1009 ◽  
Author(s):  
Jing Cao ◽  
Brian T. Steffen ◽  
Matthew Budoff ◽  
Wendy S. Post ◽  
George Thanassoulis ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Lipoprotein A

scholarly journals Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease

2020 ◽  
Vol 52 (4) ◽  
pp. 191-199 ◽  
Author(s):  
Alexander P. Kossar ◽  
Wanda Anselmo ◽  
Juan B. Grau ◽  
Yichuan Liu ◽  
Aeron Small ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Protein Expression ◽  
Aortic Valve Disease ◽  
Severe Aortic Stenosis ◽  
Valve Disease ◽  
Circulating Biomarkers ◽  
Calcific Aortic Valve Disease ◽  
Aortic Valve Sclerosis

Aortic valve sclerosis is a highly prevalent, poorly characterized asymptomatic manifestation of calcific aortic valve disease and may represent a therapeutic target for disease mitigation. Human aortic valve cusps and blood were obtained from 333 patients undergoing cardiac surgery ( n = 236 for severe aortic stenosis, n = 35 for asymptomatic aortic valve sclerosis, n = 62 for no valvular disease), and a multiplex assay was used to evaluate protein expression across the spectrum of calcific aortic valve disease. A subset of six valvular tissue samples ( n = 3 for asymptomatic aortic valve sclerosis, n = 3 for severe aortic stenosis) was used to create RNA sequencing profiles, which were subsequently organized into clinically relevant gene modules. RNA sequencing identified 182 protein-encoding, differentially expressed genes in aortic valve sclerosis vs. aortic stenosis; 85% and 89% of expressed genes overlapped in aortic stenosis and aortic valve sclerosis, respectively, which decreased to 55% and 84% when we targeted highly expressed genes. Bioinformatic analyses identified six differentially expressed genes encoding key extracellular matrix regulators: TBHS2, SPARC, COL1A2, COL1A1, SPP1, and CTGF. Differential expression of key circulating biomarkers of extracellular matrix reorganization was observed in control vs. aortic valve sclerosis (osteopontin), control vs. aortic stenosis (osteoprotegerin), and aortic valve sclerosis vs. aortic stenosis groups (MMP-2), which corresponded to valvular mRNA expression. We demonstrate distinct mRNA and protein expression underlying aortic valve sclerosis and aortic stenosis. We anticipate that extracellular matrix regulators can serve as circulating biomarkers of early calcific aortic valve disease and as novel targets for early disease mitigation, pending prospective clinical investigations.

scholarly journals Sex-Specific Features of Calcific Aortic Valve Disease

2020 ◽  
Vol 21 (16) ◽  
pp. 5620 ◽  
Author(s):  
Volha I. Summerhill ◽  
Donato Moschetta ◽  
Alexander N. Orekhov ◽  
Paolo Poggio ◽  
Veronika A. Myasoedova
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Disease ◽  
The Elderly ◽  
Developed Countries ◽  
Left Ventricular ◽  
Valve Disease ◽  
Calcific Aortic Valve Disease ◽  
Men And Women ◽  
Increased Risk

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in developed countries predominantly affecting the elderly population therefore posing a large economic burden. It is a gradually progressive condition ranging from mild valve calcification and thickening, without the hemodynamic obstruction, to severe calcification impairing leaflet motion, known as aortic stenosis (AS). The progression of CAVD occurs over many years, and it is extremely variable among individuals. It is also associated with an increased risk of coronary events and mortality. The recent insights into the CAVD pathophysiology included an important role of sex. Accumulating evidence suggests that, in patients with CAVD, sex can determine important differences in the relationship between valvular calcification process, fibrosis, and aortic stenosis hemodynamic severity between men and women. Consequently, it has implications on the development of different valvular phenotypes, left ventricular hypertrophy, and cardiovascular outcomes in men and women. Along these lines, taking into account the sex-related differences in diagnosis, prognosis, and treatment outcomes is of profound importance. In this review, the sex-related differences in patients with CAVD, in terms of pathobiology, clinical phenotypes, and outcomes were discussed.

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